Proteomics Unit, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
Department of Research, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
Sci Rep. 2020 Sep 29;10(1):16029. doi: 10.1038/s41598-020-72104-5.
A large proportion of end-stage renal disease (ESRD) patients under long-term haemodialysis, have persistent anaemia and require high doses of recombinant human erythropoietin (rhEPO). However, the underlying mechanisms of renal anaemia have not been fully elucidated in these patients. In this study, we will be focusing on anaemia and plasma proteins in ESRD patients on high-flux haemodialysis (HF) and on-line haemodiafiltration (HDF), to investigate using two proteomic approaches if patients undergoing these treatments develop differences in their plasma protein composition and how this could be related to their anaemia. The demographic and biochemical data revealed that HDF patients had lower anaemia and much lower rhEPO requirements than HF patients. Regarding their plasma proteomes, HDF patients had increased levels of a protein highly similar to serotransferrin, trypsin-1 and immunoglobulin heavy constant chain alpha-1, and lower levels of alpha-1 antitrypsin, transthyretin, apolipoproteins E and C-III, and haptoglobin-related protein. Lower transthyretin levels in HDF patients were further confirmed by transthyretin-peptide quantification and western blot detection. Since ESRD patients have increased transthyretin, a protein that can aggregate and inhibit transferrin endocytosis and erythropoiesis, our finding that HDF patients have lower transthyretin and lower anaemia suggests that the decrease in transthyretin plasma levels would allow an increase in transferrin endocytosis, contributing to erythropoiesis. Thus, transthyretin could be a critical actor for anaemia in ESRD patients and a novel player for haemodialysis adequacy.
很大一部分长期接受血液透析治疗的终末期肾病（ESRD）患者存在持续性贫血，需要使用高剂量重组人促红细胞生成素（rhEPO）。然而，这些患者的肾性贫血的潜在机制尚未完全阐明。在这项研究中，我们将重点研究高通量血液透析（HF）和在线血液透析滤过（HDF）治疗的 ESRD 患者的贫血和血浆蛋白，以使用两种蛋白质组学方法研究接受这些治疗的患者的血浆蛋白组成是否存在差异，以及这种差异如何与他们的贫血相关。人口统计学和生化数据显示，HDF 患者的贫血程度较低，rhEPO 的需求也远低于 HF 患者。关于他们的血浆蛋白质组，HDF 患者的一种与血清转铁蛋白高度相似的蛋白质、胰蛋白酶-1 和免疫球蛋白重链 alpha-1 的水平升高，而 alpha-1 抗胰蛋白酶、转甲状腺素蛋白、载脂蛋白 E 和 C-III 以及结合珠蛋白相关蛋白的水平降低。HDF 患者的转甲状腺素蛋白水平较低，通过转甲状腺素肽定量和 Western blot 检测进一步得到证实。由于 ESRD 患者的转甲状腺素蛋白水平升高，这种蛋白质可以聚集并抑制转铁蛋白内吞和红细胞生成，我们发现 HDF 患者的转甲状腺素蛋白水平较低，贫血程度较低，这表明转甲状腺素蛋白血浆水平的降低会增加转铁蛋白的内吞作用，从而促进红细胞生成。因此，转甲状腺素蛋白可能是 ESRD 患者贫血的关键因素，也是血液透析充分性的新参与者。
